We propose to develop an HIV Prevention Trials Unit (PTU) that will conduct domestic HIV Prevention Trials Network (HPTN) studies in Harlem and the South Bronx, two communities in New York City that have been severely impacted by the HIV epidemic in the United States. The proposed program, PRIDE NYC Program, will recruit populations that are currently at the highest risk for HIV infection in the US: African Americans, Hispanics, substance users and women. The PRIDE NYC Program is a consortium of four sites: Harlem Hospital Center, the New York Blood Center, Bronx-Lebanon Hospital Center and the New York Academy of Medicine. This consortium brings together two New York City HIVNET sites and two new sites. The two HIVNET sites, located at the New York Blood Center and Bronx-Lebanon Hospital Center, have demonstrated the ability to recruit and retain cohorts of substance users, women at high risk and men who have sex with men. The two new sites, at Harlem Hospital Center and the New York Academy of Medicine, have years of experience in the conduct of studies in similar groups of participants and have access to large populations appropriate for the proposed PTN studies. In response to the science agenda formulated by the HPTN Leadership Group, the PRIDE NYC Program will begin its activities by recruiting a total of 800 participants to contribute to the PTN domestic agenda on injection drug users, microbicides, behavioral interventions in women and the effect of antiretroviral therapy on transmission of HIV in discordant couples. In addition, recruitment and followup of the ongoing EXPLORE cohort will be continued at the New York Blood Center site. The investigators have developed a solid organizational plan and unit structure, a vigorous and vibrant community advisory board, internal quality assurance mechanisms, a dynamic recruitment and retention plan and mechanisms for communication with research sites, The investigators bring a wealth of expertise and experience that can influence and develop the HPTN scientific agenda. They have participated in multicenter research and clinical trial groups; have been key participants in various scientific working groups; have practical field experience and have developed innovative behavioral interventions and utilized creative methods to assess their effects. They bring together complementary skills and experiences as well as a shared commitment to these communities. The PRIDE NYC Program will be able to readily expand its capacity to conduct multiple efficacy studies through the collaborative relationship in this Consortium, through access to large populations, through their demonstrated ability in building community trust and through the solid linkages they have established with community-based organizations.